Appreciation of trimetazidine treatment in experimental sepsis rat model.

INTRODUCTION: Our aim was to determine the efficacy of trimetazidine on experimental sepsis rat model. MATERIAL AND METHODS: Sixty rats were randomized into three groups. In Group 1, sepsis was induced. In Group 2, sepsis was induced and as a therapeutic agent trimetazidine was given. In Group 3, rats were sham operated. Serum interleukin-1 beta (IL-1ß), tumor necrosis factor alfa (TNF-α), superoxide dismutase (SOD), glutathion peroxidase (GSH-Px) and malondialdehyde (MDA) levels were determined in all groups. RESULTS: In Group 2, serum GSH-Px and SOD levels were statistically significantly higher than in Group 1 (p< 0.05) and serum MDA levels were statistically significantly lower than in group 1 (p < 0.05). Trimetazidine also significantly decreased the levels of IL-1ß and TNF-a which are the proinflammatory cytokines (p < 0.05). CONCLUSION: Trimetazidine treatment significantly improved inflammation, oxidative stress and membrane destruction in LPS-induced sepsis. As the proinflammatory cytokines are supposed to play a primary role in the pathogenesis of sepsis, we assumed that the trimetazidine treatment would give new insights into the treatment of sepsis (Tab. 1, Fig. 5, Ref. 29).

Inhibition of inducible nitric oxide synthase reduces bacterial translocation in a rat model of acute pancreatitis.

INTRODUCTION: Translocation of bacteria from the gut into pancreatic necrosis is an important factor in the development of septic complications and mortality in acute pancreatitis. S-methylisothiourea (SMT) is an inducible nitric oxide synthase inhibitor that has been shown to decrease bacteria] translocation in sepsis and thermal injury. AIM: To investigate whether SMT could affect bacterial translocation in acute necrotizing pancreatitis. METHODOLOGY: Forty-five Sprague-Dawley rats were studied. Acute pancreatitis was induced in Group I and Group II by injection of taurocholate and trypsin into the common biliopancreatic duct. Group III underwent laparotomy with the manipulation (but not cannulation) of the pancreas and received saline injection. Group I rats received normal saline as a placebo, and Group II rats received SMT after surgery for 2 days. At 48 hours, blood was drawn for serum amylase determinations. Bacterial translocation to mesenteric lymph nodes and distant sites (pancreas, liver, and peritoneum) were examined. A point scoring system of histologic features was used to evaluate the severity of pancreatitis. RESULTS: Plasma amylase levels and pancreatic histologic score were significantly reduced in Group II rats given SMT compared with those in Group I rats given saline (p < 0.01, p < 0.05, respectively). All Group I rats had bacterial translocation to mesenteric lymph nodes compared with 7 of 12 rats in Group II (p < 0.05). There was no difference in bacterial translocation to distant organs between the two groups, although rates tended to be lower in Group II compared with Group I (p > 0.05). Bacterial counts in the pancreas were significantly reduced in Group II rats compared with those in Group I rats (p < 0.05). CONCLUSION: Treatment with SMT appears to have ameliorated the course of acute pancreatitis; however, mortality was not affected.

Insulin resistance in non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic steatohepatitis is a chronic liver disease that is capable of progressing to end-stage liver disease, but generally has a benign course. Obesity, non-insulin-dependent diabetes mellitus and hyperlipidaemia are the most common associations of the disease. AIMS: To investigate the insulin resistance in patients with non-alcoholic steatohepatitis who have no other causes of insulin resistance such as obesity, diabetes mellitus, and hyperlipidaemia. PATIENTS: Thirteen patients (7 male, 6 female) with non-alcoholic steatohepatitis and 12 (6 male, 6 female) healthy volunteers. METHODS: All patients and healthy volunteers were submitted to biochemical tests and hyperinsulinaemic euglycaemic insulin clamp technique. RESULTS: Basal insulin levels and C-peptide levels were significantly higher in non-alcoholic steatohepatitis group than in controls (p<0.001 and p<0.001, respectively). Hyperinsulinaemic euglycaemic insulin clamp technique revealed lower glucose utilization in the non-alcoholic steatohepatitis group and the difference was statistically significant (p<0.001). CONCLUSIONS: Our study revealed marked hyperinsulinaemia and insulin resistance in patients with non-alcoholic steatohepatitis. Hyperinsulinaemia and insulin resistance may contribute to pathogenesis of nonalcoholic steatohepatitis.

Effects of losartan treatment on T-cell activities and plasma leptin concentrations in primary hypertension.

Recent evidence shows that leptin may contribute to elevated blood pressure (BP) and interact with the renin-angiotensin-aldosterone and cellular immune systems. Altered T-cell activities and changes in T-cell subset ratios have also been reported in hypertension. However, little is known about the effects of AT1-receptor antagonism on T-cell activities and plasma leptin concentrations in primary hypertension. We have, therefore, investigated the relationship between leptin and T-cell activities and the effect of an AT1-receptor antagonist, losartan, in primary hypertension. Twenty recently-diagnosed and untreated young adults (11 males and 9 females, age; 39.9+/-7.6 years, range 23-49 years, BMI; 27.6+/-3.7kg/m2) and 20 normotensive healthy, age-, sex- and BMI-matched controls were studied. The [3H]-thymidine uptakes of cultured lymphocytes were determined, both spontaneously and after stimulation with phytohaemagglutinin. The tests were performed before and after three months of treatment with losartan. The results indicate that the blastogenic responses of T-cells to phytohaemagglutinin are significantly higher in the patient group compared with controls (p=0.02). After normalisation of BP, T-cell responses were significantly reduced and were lower than in the controls (p=0.01). Pretreatment plasma leptin levels were significantly higher in hypertensives than in controls (p=0.01). However, losartan treatment had no significant effect on leptin concentrations; moreover, no correlation between leptin levels and T-cell activity was found. Our data show that plasma leptin levels and T-cell activity are markedly enhanced in untreated essential hypertension and that the alteration of T-cell activity is not related to plasma leptin levels. Antihypertensive treatment with losartan decreases T-cell activities but does not influence plasma leptin levels. We conclude that leptin levels are not affected by AT1-receptor blockade and are not related to T-cell activity.

CA-125; a new marker for diagnosis and follow-up of patients with tuberculous peritonitis.

BACKGROUND: Most malignancies with peritoneal infiltration, especially ovarian cancers and chronic liver diseases associated with ascites give rise to high serum CA-125 levels. Tuberculous peritonitis is another cause for high serum CA-125 levels. AIM: To investigate the relation between serum CA-125 level and response to treatment in tuberculous peritonitis patients. PATIENTS: Ten patients with tuberculous peritonitis were enrolled in the study. METHOD: Definite diagnosis of tuberculous peritonitis was made by acid-fast smears, specific culture, and polymerase chain reaction. Serum CA-125 levels were measured before and at the fourth month of treatment. RESULTS: Before antituberculous treatment, serum CA-125 levels of all patients were very high (mean+/-SD: 475. 80+/-106. 19 U/ml) and comparable with those of patients with ovarian cancers. At the end of the fourth month of treatment, serum CA-125 levels in all patients decreased to within normal limits (<35 U/ml)(20.80:+/-5.18 U/ml) in parallel with the clinical improvement. The differences in CA125 levels before and after treatment were statistically significant (p<0.001). CONCLUSIONS: Results of our study suggest that serum CA-125 levels in patients with tuberculous peritonitis are as high as ovarian cancers associated with peritoneal infiltration. By the end of the fourth month of antituberculous therapy, serum CA-125 levels have returned to normal. We, therefore, suggest that serum CA-125 can be used to evaluate the efficacy of therapy in tuberculous peritonitis.